Adaptability and regulation of the ubiquitin-proteasome system
Abstract/Contents
- Abstract
- Aging, disease, and environmental stressors are associated with failures in the ubiquitin-proteasome system (UPS), yet a quantitative understanding of how the UPS senses and addresses proteotoxic stressors is lacking. We assessed UPS performance and adaptability in yeast under stressors using quantitative measurements of the proteolytic stress response (PSR), a transcriptional program driven by the protein Rpn4 that expresses the UPS. We found that the UPS productively adapts to different proteotoxic stressors using separate mechanisms. Proteolytic stressors cause Rpn4 stabilization while folding stressors increase RPN4 transcription without increasing UPS demand. We also probed the genome for modulators of the PSR using the reverse genetic method ReporterSeq. We identified several PSR regulators, including thioredoxin reductase (Trr1), which had no known role in UPS regulation. Unlike all known mechanisms for Rpn4 regulation, which regulate Rpn4 levels, we found that Trr1 modulates the molecular activity of Rpn4 and does so in response to oxidative stress. Together, this work reveals the distinct effects of proteotoxic stressors on the UPS and illuminates the genetic landscape through which cells signal it.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Work, Jeremy Julian |
|---|---|
| Degree supervisor | Brandman, Onn |
| Thesis advisor | Brandman, Onn |
| Thesis advisor | Ferrell, James Ellsworth |
| Thesis advisor | Jarosz, Daniel |
| Thesis advisor | Krasnow, Mark, 1956- |
| Degree committee member | Ferrell, James Ellsworth |
| Degree committee member | Jarosz, Daniel |
| Degree committee member | Krasnow, Mark, 1956- |
| Associated with | Stanford University, Department of Biochemistry |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Jeremy Julian Work. |
|---|---|
| Note | Submitted to the Department of Biochemistry. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/bf367nn3895 |
Access conditions
- Copyright
- © 2021 by Jeremy Julian Work
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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